Postoperative Cesarean Section Pain Management Using Transversus Abdominis Plane Block Versus Intrathecal Morphine: A Systematic Review and Meta-analysis.

PURPOSE: Compare and evaluate the effectiveness of transversus abdominis plane (TAP) block versus intrathecal morphine (ITM) on elective postcesarean section pain, opioid consumption, and related side effects. DESIGN: Systematic review and meta-analysis. METHODS: A search for evidence was conducted in PubMed, Google Scholar, CINAHL, Cochrane Collaboration Database, UpToDate, Health Source, and gray literature. Only randomized controlled trials (RCTs) were included in the study. The methodological quality of evidence assessment was conducted using the Risk of Bias and Grades of Recommendation, Assessment, Development, and Evaluation system. The meta-analysis used Review Manager (RevMan 5.4, The Cochrane Collaboration). FINDINGS: A total of 11 RCTs involving 1,129 patients were analyzed. Compared to ITM, TAP has a similar effect on static (mean difference [MD]; 0.37; 95% confidence interval [CI], -0.04 to 0.79; P = .08) and dynamic pain scores (MD, 0.43; 95% CI, -0.06 to 0.92; P = .09) within the first 48 hours after surgery. Additionally, the TAP block had a lower incidence of postoperative nausea and vomiting (risk ratio, 0.45; 95% CI, 0.31 to 0.66; P < .0001) and increased opioid consumption (MD, 6.78; 95% CI, 3.79 to 9.77; P < .00001). Overall, TAP block and ITM did not differ in the time to first to rescue analgesia, incidence of sedation, and pruritus. CONCLUSIONS: Evidence suggests that TAP blocks are equivalent to ITM in pain scores and more effective at lowering the incidence of postoperative nausea and vomiting, yet ITM has been shown to be more effective in reducing postoperative opioid consumption.

Pre-competition body mass loss characteristics of Brazilian jiu-jitsu competitors in the United Kingdom.

BACKGROUND: Brazilian jiu-jitsu (BJJ) is a grappling-based combat sport in which competitors engage in pre-competition acute 'weight' loss (AWL) and rapid 'weight' loss (RWL) to achieve the body mass (BM) required for their desired division. AWL/RWL practices of UK BJJ competitors have not previously been reported. AIM: Our aim in this study was to determine the prevalence, magnitude and stakeholder influences of AWL and RWL amongst BJJ participants in the United Kingdom (UK). A secondary aim was to explore whether there is any influence of time spent in the sport or competition frequency on AWL/RWL practices. METHODS: In this study we used the rapid weight loss questionnaire (RWLQ) adapted for BJJ to determine the prevalence and magnitude of AWL/RWL in UK BJJ, the prevalence of methods used and the key stakeholder influences on these practices. As a secondary investigation we aimed to determine whether there was any effect of age starting BJJ on AWL/RWL. RESULTS: Of 115 completed responses, 59% stated they performed AWL/RWL before competition. Mean BM loss for this competition was 1.9 ± 3.8 kg (2.3 ± 4.6%), with 34% of participants starting BM loss 3-7 days prior and 16% starting 0-2 days prior. Methods used tend to be achieving calorie deficit via exercise and diet rather than hypohydration, with little advice from formally qualified personnel. Participants who perform AWL/RWL started training (BF10 = 199, d = .72) and competing (BF10 = 107, d = .68) in BJJ younger than those who do not perform AWL/RWL. CONCLUSIONS: AWL/RWL is prevalent in UK BJJ, but not at the magnitude of other combat sports or countries. Though negative effects of extreme hypohydration are unlikely, there may be a higher chance of eating disorders in BJJ, particularly due to the young age of AWL/RWL commencement.

"There are still a lot of things that I need": a qualitative study exploring opportunities to improve the health services of First Nations People with arthritis seen at an on-reserve outreach rheumatology clinic.

BACKGROUND: Arthritis is a highly prevalent disease and leading cause of disability in the Indigenous population. A novel model of care consisting of a rheumatology outreach clinic in an on-reserve primary healthcare center has provided service to an Indigenous community in Southern Alberta since 2010. Despite quality assessments suggesting this model of care improves accessibility and is effective in meeting treatment targets, substantial improvements in patient-reported outcomes have not been realized. Therefore, the objective of this study was to explore the experiences of Indigenous persons with arthritis and healthcare providers involved in this model of care to inform the development of health service improvements that enhance patient outcomes. METHODS: This was a narrative-based qualitative study involving a purposeful sample of 32 individuals involved in the Indigenous rheumatology model of care. In-depth interviews were conducted to elicit experiences with the existing model of care and to encourage reflections on opportunities to improve it. A two-stage analysis was conducted. The first stage aimed to produce a narrative synthesis of concepts through a dialogical method comparing people with arthritis and health providers' narratives. The second stage involved a collective effort to synthesize concepts and propose specific recommendations to improve the quality of the current model of care. Triangulation, through participant checking and discussion among researchers, was used to increase the validity of the final recommendations. RESULTS: Ten Indigenous people with arthritis lived experience, 14 health providers and 8 administrative staff were interviewed. One main overarching theme was identified, which reflected the need to provide services that improve people's physical and mental functioning. Further, the following specific recommendations were identified: 1) enhancing patient-provider communication, 2) improving the continuity of the healthcare service, 3) increasing community awareness about the presence and negative impact of arthritis, and 4) increasing peer connections and support among people living with arthritis. CONCLUSIONS: Improving the quality of the current Indigenous rheumatology model of care requires implementing strategies that improve functioning, patient-provider communication, continuity of care, community awareness and peer support. A community-based provider who supports people while navigating health services could facilitate the implementation of these strategies.

Mental Health Symptoms and Parenting Among Father-Only and Dual Substance Use Disorder Couples.

In the present study, we examined associations between fathers' and mothers' mental health symptoms as related to their own and their partner's parenting in couples in which fathers (n = 38 families) or both partners (n = 30 families) had substance use disorder (SUD). Each partner reported on symptoms of depression, anxiety, and hostility; children reported on each parent's parenting behaviors, including acceptance, psychological control, and knowledge of children. Actor-partner interdependence models indicated that when substance-abusing fathers have more symptoms of anxiety and depression, non-substance-abusing mothers report greater knowledge of children, whereas non-substance-abusing mothers' mental health symptoms were related to less paternal knowledge of children. In dual SUD couples, mothers' depressive symptoms were associated with more paternal knowledge of children. These preliminary findings offer select support for family systems theory.

Acceptability of aggression among children who reside with substance-abusing parents: The influence of behavioral dysregulation, exposure to neighborhood violence, and interparental violence.

The present study examined how interparental violence, neighborhood violence, behavioral regulation during parental conflict, and age predicted beliefs about the acceptability of aggression and the acceptance of retaliation against an aggressive peer among youths. Participants were 110 families (mothers, fathers, and children) in which one or both parents met criteria for substance use disorder. Results of a bootstrapped path model revealed higher exposure to neighborhood violence predicted greater acceptability of general aggression, whereas higher father-to-mother violence perpetration predicted lower acceptability of general aggression. Higher exposure to neighborhood violence, behavioral dysregulation during parental conflict, and older child age predicted greater approval of retaliation toward an aggressive peer. Findings are interpreted as related to the cognitive-contextual framework.

Low wear rates seen in THAs with highly crosslinked polyethylene at 9 to 14 years in patients younger than age 50 years.

BACKGROUND: Patients 50 years or younger are at high risk for wear-related complications of their total hip arthroplasty (THA) because of their generally higher levels of activity. Highly crosslinked polyethylene (HXLPE) is believed to be more durable for this population than conventional polyethylene because of its improved wear; however, limited information is available on the wear of HXLPE in this population, particularly the wear of HXLPE when it articulates with alternative bearings like Oxinium (Smith & Nephew, Memphis, TN, USA). QUESTIONS/PURPOSES: The purpose of this study was to evaluate two questions relative to this population of patients undergoing THA. First, what was the linear and volumetric wear rate of HXLPE in patients 50 years or younger at a minimum followup of 9 years and was osteolysis observed in any of these hips? Given the potential for damage to the Oxinium femoral head surface, was the wear of HXLPE in the patients with this material similar to the other bearings or was there accelerated or runaway wear that was visible in any of the patients? METHODS: From November 1999 to April 2005, 105 THAs were performed in 95 patients 50 years of age or younger (mean, 42 years; range, 20-50 years). The mean body mass index was 30 kg/m(2) (range, 17-51 kg/m(2)).The mean followup was 12 years (range, 9-14 years). Two patients died, five patients (one bilateral) were lost to followup, and one hip was revised elsewhere for pain. The patients' information was not included in the study, which left 87 patients with 96 hips for analysis. Highly crosslinked polyethylene was the acetabular bearing for all of the hips. We analyzed the linear and volumetric wear of all of the hips using the Martell method. Eighty hips had the same diameter head (28 mm) allowing us to more accurately compare the different bearing materials. The type of femoral head used was related to our sequential use of materials beginning with cobalt chrome (14), ceramic (23) followed by Oxinium (43) in the hips with 28-mm heads. Although cobalt-chrome was used early in this study, our previous experience with ceramic on polyethylene encouraged us to use it as an alternative bearing. The Oxinium was used consecutively for the remaining hips. RESULTS: The mean wear of the HXLPE after 1 year of bedding-in (true linear wear)was 0.022 mm/year (95% confidence interval [CI], 0.015-0.030 mm/year). The mean volumetric wear of HXLPE after 1 year of bedding-in (true volumetric wear) was 9 mm(3)/year (95% CI, 4-14 mm(3)/year). None of the hip radiographs had evidence of loosening or osteolysis. Wear was not associated with femoral head material (p = 0.58 for linear wear/year versus head material and p = 0.52 for volumetric wear/year versus head material). CONCLUSIONS: In our study of patients 50 years of age or younger undergoing THA, the linear and volumetric wear rates of HXLPE were very low regardless of the bearing surface material. The laboratory concerns of Oxinium surface damage are serious but at this time we have not seen high wear of the HXLPE or osteolysis in this population. LEVEL OF EVIDENCE: Level III, therapeutic study.

Factors Associated With Hospital Admission in the Last Month: A Retrospective Single Center Analysis.

CONTEXT: Driven by concerns about care quality, patient experience, and national metrics, health systems are increasingly focusing on identifying risk factors for patients who are hospitalized in the last month of life. OBJECTIVE: To evaluate patient factors associated with hospital admission in the last month (30 days). METHODS: We analyzed a retrospective cohort of 8488 patients with a primary care visit in a tertiary health system in the last year of life using a linked electronic health record and decedent dataset. We examined healthcare utilization (primary care, emergency, hospital, intensive care unit encounters) and end-of-life related outcomes (palliative care consultation, do-not-resuscitate orders, advance care planning documentation, hospice at hospital discharge, death in health system). Multivariable logistic regressions identified patient factors associated with admission in the last month. RESULTS: About 2202 (25.9%) patients had a hospital admission in the last month. Among the 1282 (15.1%) who died in a health system facility, most (1103/1282, 86.0%) were admitted to the hospital in the last month. Among patients with a hospital admission and discharged in the last month, 60.9% (686/1126) were discharged on hospice. Compared to those without these diseases, metastatic cancer, liver disease, or heart failure had the highest odds of admission in the last month (adjusted OR 2.36 95%CI 2.05-2.72; 2.28, 95%CI 1.98-2.62; and 2.17 95%CI 1.93-2.45 respectively). CONCLUSIONS: As patients with heart or liver disease or metastatic cancer had the highest odds of admission in the last month, collaborative interventions between primary, palliative, and specialty care may improve quality of care at the end of life.

UC-II® undenatured type II collagen data show retention during functional food and beverage prototype processing.

Nowadays, collagen is widely used in food and beverage industries to enhance the nutritional and health value of the products. While many see this as an ideal way to incorporate more collagen into their diets, the exposure of these proteins to high temperature or acidic and alkaline solutions may negatively affect the quality and activity of these supplements. In general, the manufacturing of functional food and beverages often largely depends on the stability of the active ingredients during processing. The high temperatures, humidity, and low pH of processing may reduce product nutrient retention. Hence, understanding stability of collagen is of great significance and these data were gathered to determine the extent of undenatured type II collagen retention under different processing conditions. UC-II® undenatured type II collagen is a patented form of collagen derived from chicken sternum cartilage, and different food and beverage prototypes incorporating UC-II® undenatured type II collagen were produced. The content of undenatured type II collagen was compared in their pre-and post-manufacturing formats using an enzyme-linked immunosorbent assay. The undenatured type II collagen retention varied depending upon the prototype, with the highest amount of undenatured type II collagen retention occurring in nutritional bars (approximately 100%), followed by chews (98%), gummies (96%), and dairy beverages (81%). The present work also showed that recovery of the undenatured type II collagen depends on the exposure time, temperature and pH of the prototype.

Gender Roles in the Millennium: Who Pays and Is Expected to Pay for Romantic Dates?

Research on monetary decisions and behaviors in dating relationships is very limited. The purpose of this study was to examine college students' current practice and expectations for date payment for first and subsequent romantic dates in the framework of gender role theory. A sample of 552 heterosexual college students took an online survey that included questions about their actual and expected payment for their first and subsequent dates. Participants also completed several measures regarding their gender roles. The findings indicated that traditional gender norms in dating continue to be popular in the new millennium because in actual practice, men almost always paid the whole bill of the first dates and paid more for subsequent dates. When asked who should pay for the dates, participants also expected men to pay more for first and subsequent dates. Women did show some willingness to share date expenses, although nowhere close to be completely even. The findings also indicated that gender role attitudes played little role in actual practice but had a stronger role in date payment expectations, showing that individuals subscribing to traditional gender inequality views tended to believe that men should pay more for dates.

Predicting Chinese Adolescents' Depressive Symptoms from Their Cultural Orientations and Perceived Parental Psychological Control.

Research on adolescents across cultures has suggested a positive link between parental psychological control and adolescent depression. While a few studies have examined psychological outcomes of adolescents in collectivist groups compared to individualist groups, much less is known about the role of cultural orientations in the parental control-depression link at the individual level. The current study examined: (1) both mother and father psychological control as predictors of depressive symptoms in Chinese adolescents, (2) adolescents' cultural orientations of individualism and collectivism as predictors of their depressive symptoms, and (3) the moderating effects of adolescents' cultural orientations on the association between parental control and depressive symptoms. The sample included 3255 adolescents located in southern China. Adolescents reported on their orientations of individualism and collectivism, perceived mothers' and fathers' psychological control, and their depressive symptoms. Analyses revealed that both mother and father psychological control as well as adolescents' individualism were positive predictors of adolescent depressive symptoms, whereas collectivism was a negative predictor of depressive symptoms. Furthermore, the results indicated that cultural orientations had weak moderating effects on the link between parental control and adolescent depressive symptoms. Theoretical and practical implications are discussed.

Religiousness in the first year of COVID-19: A systematic review of empirical research.

The COVID-19 pandemic emerged suddenly in early 2020, posing a serious health threat and creating tremendous stress and distress across the world. Religion has been shown to play important and varied roles in previous disasters and health crises, but its roles in the pandemic have yet to be outlined. We aimed to summarize the research conducted on religion and COVID-19 in the first year of the pandemic with a systematic review of studies that specifically involved individual-level religiousness and COVID-19. Searches were conducted in PubMed, Scopus, CINAHL, and PsycINFO covering a one-year period from the first published mention of the novel coronavirus (Jan. 5, 2020) through January 4, 2021. We included articles about COVID-19 that were peer-reviewed and empirical, measured and reported results on religion on an individual level, and were available in English. Our search produced 137 empirical articles that met the inclusion criteria. In the course of sorting studies by their primary focus, eight categories of empirical findings emerged: general distress and wellbeing (53 articles), COVID-19-specific stress (24 articles), beliefs in science, conspiracies, and misinformation (15 articles), COVID-19 public health behaviors (12 articles), perceived risk of COVID-19 (10 articles), perceived growth or positive changes taking place during the pandemic (nine articles), health behaviors (three articles), and consumer behavior (three articles). Findings indicated that religiousness was associated with both unique benefits and challenges and played a significant role in the pandemic. Religiousness was associated with a broad range of outcomes across geographical regions and populations during the first year of COVID-19. It was a commonly reported coping mechanism with varying levels of favorable associations with mental health and COVID-19-related behaviors.

Propelled by the Pandemic: Responses and Shifts in Primary Healthcare Models for Indigenous Peoples.

The COVID-19 pandemic posed a significant risk to the health and well-being of First Nations and Métis communities in Alberta. Communities' self-determined and integrated responses with embedded cultural supports - in collaboration with governments, organizations and providers - were key to minimizing morbidity and mortality. Maintaining and building these relationships in the continued pandemic response, broadening approaches to healthcare delivery and continuing to include culture will support attainment of the Indigenous primary healthcare model while addressing logistical challenges in transforming and sustaining healthcare systems in the background of ongoing inequities in the social determinants of health.

Redesigning Care of Hospitalized Young Adults With Chronic Childhood-Onset Disease.

Background Young adults with chronic childhood-onset disease (CCOD) are routinely admitted to internal medicine hospitalist services, yet most lack transition preparation to adult care. Providers and patients feel the strain of admissions to adult services in part due to their medical and social complexity. Methods We performed a descriptive study of a care redesign project for young adults with CCOD hospitalized at a large, tertiary care academic hospital. We describe the process of implementation of the Med-Peds (MP) service line and characterize patients cared for by the service. We measured and analyzed patient demographics, process implementation, healthcare screening, and healthcare utilization data. Results During the 16 months of the study period, 254 patients were cared for by the MP service line, accounting for 385 hospitalizations. The most common CCODs were sickle cell disease (22.4%) and type 1 diabetes (14.6%). The majority (76%) of patients completed transition readiness assessment, and 38.6% completed social determinant of health (SDH) screening during their admission. Patients had high prevalence of SDH with 66.7% having an unmet social need. The average length of stay was 6.6 days and the average 30-day readmission rate was 20.0%. Conclusions There is opportunity to redesign the inpatient care of young adult patients with CCOD. The MP service line is a care model that can be integrated into existing hospital medicine teams with MP physicians. Hospitals should consider redesigning care for young adults with CCOD to meet the transitional and social needs unique to this patient population.

Review of topical gelatin-based haemostatic agents; an insidious culprit of intraoperative anaphylaxis?

BACKGROUND: An under-recognized complication of gelatin-based haemostatic agents is their potential to cause anaphylactic reactions. This review aims to collate and analyse case in the literature of intraoperative anaphylaxis secondary to locally applied haemostatic agents. METHODS: An electronic search was performed on databases Medline, Embase, Pubmed and ProQuest. A total of 7671 articles were reviewed from title and abstract. After exclusion criteria and duplicates removed, 19 articles with 21 cases were included for analysis. Data extracted from each of the articles included patient demographics, haemostatic agent used, surgery type, known allergies and any objective evidence of hypersensitivity post anaphylactic episode, that is tryptase levels, IgE levels, skin prick testing. RESULTS: Fifty-seven percent of cases involved patients <18 years of age; 57% of cases involved spinal surgery; 100% of cases displayed objective evidence of hypersensitivity (tryptase levels, bovine or porcine IgE levels, or skin prick testing). Thirty-three percent of patients had exposure preoperatively to a known agent causing anaphylaxis or allergy which would preclude the use of a gelatin-based haemostat. These products included vaccines, spam meats, red meat, Jell-O and CollaPlug. Gelatin-based haemostat agents included Floseal, Gelfoam, Surgiflo, fibrin glue, Avitene, haemofibrine sponge, topical bovine thrombin and thrombin-soaked gelatin. CONCLUSION: Increased awareness of allergy to gelatin-based haemostats for surgical and anaesthetic is imperative, with 33% of cases having a known contraindication to gelatin-based haemostat. This review highlights important aspects in the pre-operative patient history and post-event patient investigation that could assist anaesthetists and surgeons in the prevention of future events.

Relating Gender to Sex: Gendered Attitudes, Sexual Double Standard, Sexual Intentions and Behaviors in two Chinese Adolescent Samples.

Adolescence is a critical life stage when individuals further consolidate their gender role concepts, develop sexual beliefs, and likely begin to experiment with sexual behaviors. While there have been numerous studies on adolescents' gender role attitudes, sexual beliefs, and sexual behaviors, the bulk of this research has been based on Western samples. The current study aimed to expand our knowledge of adolescents' gender and sexuality by examining gender role attitudes, sexual beliefs, and sexual behaviors in an urban sample (n = 613) and a rural sample (n = 408) from China. Adolescent boys reported stronger identification with the negative male role, less sexual guilt, and stronger sexual intention than their female counterparts. Compared to the urban sample, adolescents in the rural sample were more likely to endorse both negative and positive male roles, hold the sexual double standard, and experience sexual guilt. Regression analyses yielded significant interaction effects between sex and negative male role on sexual guilt and sexual intention, suggesting that the negative male role was differentially associated with sexual guilt and sexual intention in boys versus in girls. Moreover, the negative male role was the only significant predictor of sexual behavior. Cultural implications of these findings were discussed.

Arthritis liaison: a First Nations community-based patient care facilitator. / Agente de liaison avec les personnes atteintes d'arthrite : un rôle important dans la prestation de soins à des patients des collectivités des Premières Nations.

INTRODUCTION: Arthritis is a leading cause of disability in First Nations communities and is often accompanied by other chronic diseases. Existing care models prioritize accessibility to specialty care for treatment, whereas patient-centred approaches support broader health goals. METHODS: A patient care facilitator model of care, termed "arthritis liaison," was developed with the community to support culturally relevant patient-centred care plans. Following a one-year-long intervention, we report on the feasibility and acceptability of this care model from the perspectives of patients and health care providers. RESULTS: The arthritis liaison served as a bridge between the clinicians and patients, and fostered continuity, helping patients receive coordinated care within the community.

Bioavailability of a Capsaicin Lipid Multi-particulate Formulation in Rats.

BACKGROUND AND OBJECTIVE: Because of the stomach-burning sensation it induces, capsaicin has been used at relatively low doses as a nutritional supplement, which has limited its bioavailability. The objective of this study was to investigate the serum bioavailability of capsaicin supplementation with or without a lipid multi-particulate (LMP) formulation. METHODS: Thirty-five rats were divided into five groups and administered capsaicin at either 0.2 or 1 mg/kg with or without the LMP formulation. Capsaicin bioavailability was assessed based on the area under the concentation-time curve (AUC), the time to peak concentration (Tmax), and the peak serum concentration (Cmax). RESULTS: For each formulation, the capsaicin Cmax was reached at 90 min and decreased thereafter. Serum capsaicin concentrations were greater in rats administered the higher dose of capsaicin (1 mg/kg) in the LMP formulation at all measurement times (P  ≤ 0.05). The AUC showed a significant increase, about 20%, when capsaicin was administered in the LMP formulation at the high dose (P = 0.002). The Tmax for oral capsaicin was similar whether or not administration was via the LMP formulation (P = 0.163). However, the Cmax of capsaicin increased in a dose-dependent manner (P < 0.05). Although the LMP formulation of the high dose of capsaicin resulted in a numerically higher Cmax, it was not statistically significantly higher (P = 0.068). CONCLUSIONS: The present work demonstrated that administration of capsaicin via the LMP formulation significantly impacted the pharmacokinetic parameters and the serum bioavailability of orally administered 1 mg/kg capsaicin in rats. The bioavailability of capsaicin in humans may also be increased by using the LMP formulation.

Comparison of protection and release behavior of different capsule polymer combinations based on L. acidophilus survivability and function and caffeine release.

Oral administration of active pharmaceutical ingredients, nutraceuticals, enzymes or probiotics requires an appropriate delivery system for optimal bioactivity and absorption. The harsh conditions during the gastrointestinal transit can degrade the administered products, hampering their efficacy. Enteric or delayed-release pharmaceutical formulations may help overcome these issues. In a Simulator of Human Intestinal Microbial Ecosystem model (SHIME) and using caffeine as a marker for release kinetics and L. acidophilus survivability as an indicator for protection, we compared the performance of ten capsule configurations, single or DUOCAP® combinations. The function of L. acidophilus and its impact on the gut microbiota was further tested in three selected capsule types, combinations of DRcaps® capsule in DRcaps® capsule (DR-in-DR) and DRcaps® capsule in Vcaps® capsule (DR-in-VC) and single Vcaps® Plus capsule under colonic conditions. We found that under stomach and small intestine conditions, DR-in-DR and DR-in-VC led to the best performance both under fed and fasted conditions based on the slow caffeine release and the highest L. acidophilus survivability. The Vcaps® Plus capsule however, led to the quickest caffeine and probiotic release. When DR-in-DR, DR-in-VC and single Vcaps® Plus capsules were tested through the whole gastrointestinal tract, including under colonic conditions, caffeine release was found to be slower in capsules containing DRcaps® capsules compared to the single Vcaps® capsules. In addition, colonic survival of L. acidophilus was significantly increased under fasted conditions in DR-in-DR or DR-in-VC formulation compared to Vcaps® Plus capsule. To assess the impact of these formulations on the microbial function, acetate, butyrate and propionate as well as ammonia were measured. L. acidophilus released from DR-in-DR or DR-in-VC induced a significant increase in butyrate and a decrease in ammonia, suggesting a proliferation of butyrate-producing bacteria and reduction in ammonia-producing bacteria. These data suggest that L. acidophilus included in DR-in-DR or DR-in-VC reaching the colon is viable and functional, potentially contributing to changes in colonic microbiota composition and diversity.

Effects of Low Doses of L-Carnitine Tartrate and Lipid Multi-Particulate Formulated Creatine Monohydrate on Muscle Protein Synthesis in Myoblasts and Bioavailability in Humans and Rodents.

The primary objective of this study was to investigate the potential synergy between low doses of L-carnitine tartrate and creatine monohydrate to induce muscle protein synthesis and anabolic pathway activation in primary human myoblasts. In addition, the effects of Lipid multi-particulates (LMP) formulation on creatine stability and bioavailability were assessed in rodents and healthy human subjects. When used individually, L-carnitine tartrate at 50 µM and creatine monohydrate at 0.5 µM did not affect myoblast protein synthesis and signaling. However, when combined, they led to a significant increase in protein synthesis. Increased AKT and RPS6 phosphorylation were observed with 50 µM L-carnitine tartrate 5 µM creatine in combination in primary human myoblasts. When Wistar rats were administered creatine with LMP formulation at either 21 or 51 mg/kg, bioavailability was increased by 27% based on the increase in the area under the curve (AUC) at a 51 mg/kg dose compared to without LMP formulation. Tmax and Cmax were unchanged. Finally, in human subjects, a combination of LMP formulated L-carnitine at 500 mg (from L-carnitine tartrate) with LMP formulated creatine at 100, 200, or 500 mg revealed a significant and dose-dependent increase in plasma creatine concentrations. Serum total L-carnitine levels rose in a similar manner in the three combinations. These results suggest that a combination of low doses of L-carnitine tartrate and creatine monohydrate may lead to a significant and synergistic enhancement of muscle protein synthesis and activation of anabolic signaling. In addition, the LMP formulation of creatine improved its bioavailability. L-carnitine at 500 mg and LMP-formulated creatine at 200 or 500 mg may be useful for future clinical trials to evaluate the effects on muscle protein synthesis.

The Effect of Capsule-in-Capsule Combinations on In Vivo Disintegration in Human Volunteers: A Combined Imaging and Salivary Tracer Study.

Controlling the time point and site of the release of active ingredients within the gastrointestinal tract after administration of oral delivery systems is still a challenge. In this study, the effect of the combination of small capsules (size 3) and large capsules (size 00) on the disintegration site and time was investigated using magnetic resonance imaging (MRI) in combination with a salivary tracer technique. As capsule shells, Vcaps® HPMC capsules, Vcaps® Plus HPMC capsules, gelatin and DRcaps® designed release capsules were used. The three HPMC-based capsules (Vcaps®, Vcaps® Plus and DRcaps® capsules) were tested as single capsules; furthermore, seven DUOCAP® capsule-in-capsule combinations were tested in a 10-way crossover open-label study in six healthy volunteers. The capsules contained iron oxide and hibiscus tea powder as tracers for visualization in MRI, and two different caffeine species (natural caffeine and 13C3) to follow caffeine release and absorption as measured by salivary levels. Results showed that the timing and location of disintegration in the gastrointestinal tract can be measured and differed when using different combinations of capsule shells. Increased variability among the six subjects was observed in most of the capsule combinations. The lowest variability in gastrointestinal localization of disintegration was observed for the DUOCAP® capsule-in-capsule configuration using a DRcaps® designed release capsule within a DRcaps® designed release outer capsule. In this combination, the inner DRcaps® designed release capsule always opened reliably after reaching the ileum. Thus, this combination enables targeted delivery to the distal small intestine. Among the single capsules tested, Vcaps® Plus HPMC capsules showed the fastest and most consistent disintegration.